Increased Circulating PD-1 hi CXCR5 – Peripheral T Helper Cells are Associated with Disease Activity of ANCA-Associated Vasculitis

Newly identified PD-1 hiCXCR5 –CD4 + T cells, termed as peripheral helper T cells (Tph), have been found elevated and playing pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph cells in Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph cells was greatly decreased in AAV patients after receiving treatment. Tph cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR) and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph cells frequency was also positively correlated with naïve B cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21 and IL-12. However, serum IL-10 exhibited negative correlation with circulating Tph cells in active AAV patients. These results demonstrated that circulating Tph cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV.

Therapeutic and Pharmaceutical Potential of Cinnamon

Cinnamon has been used as a spice, condiment, and aromatic plant since centuries ago. Cinnamon is a small evergreen tree belonging to the genus Cinnamomum in the family Lauraceae. There are more than 250 species of cinnamon worldwide. In India, Cinnamomum verum and Cinnamomum cassia are the most common species grown in the Himalaya region. They have been used as folk medicine for the treatment of nausea, flatulent dyspepsia, coughs, diarrhea, malaria, gastric disorder, and to alleviate pain and inflammation in rheumatic arthritis. Therapeutic properties of cinnamon are due to the presence of bioactive constituents such as p-coumaric, cinnamaldehyde, cinnamic acid, and eugenol. Cinnamaldehyde and eugenol are the major active constituents responsible for its characteristic flavor, aroma, and therapeutic properties. Pharmacological studies found that it could be a promising candidate with potential for designing new drugs. This review is aimed to summarize the ethanomedicinal importance, phytochemistry, and wide spectrum of pharmacological and therapeutic applications of cinnamon.

On the use of tissue hydrophilicity test for rheumatism in children

The test for the hydrophilicity of tissues according to McClure, which is reduced to the intradermal administration of 0.2 saline and monitoring the time of resorption of the blister formed in this case, has already been used for rheumatism in children (O. K-Miss), and its acceleration in the acute period has been shown rheumatism up to 15-40 minutes, whereas normally its time ranges from 30 minutes. in infants up to 52 minutes. - at an older age (MS Maslov), The most significant acceleration of it was observed in violent rheumatic arthritis and in severe acute period with severe symptoms of heart failure.

Gaultheria leucocarpa var. yunnanensis for Treating Rheumatoid Arthritis—An Assessment Combining Machine Learning–Guided ADME Properties Prediction, Network Pharmacology, and Pharmacological Assessment

Background: Dianbaizhu (Gaultheria leucocarpa var. yunnanensis), a traditional Chinese/ethnic medicine (TC/EM), has been used to treat rheumatoid arthritis (RA) for a long time. The anti–rheumatic arthritis fraction (ARF) of G. yunnanensis has significant anti-inflammatory and analgesic activities and is mainly composed of methyl salicylate glycosides, flavonoids, organic acids, and others. The effective ingredients and rudimentary mechanism of ARF remedying RA have not been elucidated to date.Purpose: The aim of the present study is to give an insight into the effective components and mechanisms of Dianbaizhu in ameliorating RA, based on the estimation of the absorption, distribution, metabolism, and excretion (ADME) properties, analysis of network pharmacology, and in vivo and in vitro validations.Study design and methods: The IL-1β–induced human fibroblast-like synoviocytes of RA (HFLS-RA) model and adjuvant-induced arthritis in the rat model were adopted to assess the anti-RA effect of ARF. The components in ARF were identified by using UHPLC-LTQ-Orbitrap-MSn. The quantitative structure–activity relationship (QSAR) models were developed by using five machine learning algorithms, alone or in combination with genetic algorithms for predicting the ADME properties of ARF. The molecular networks and pathways presumably referring to the therapy of ARF on RA were yielded by using common databases and visible software, and the experimental validations of the key targets conducted in vitro.Results: ARF effectively relieved RA in vivo and in vitro. The five optimized QSAR models that were developed showed robustness and predictive ability. The characterized 48 components in ARF had good biological potency. Four key signaling pathways were obtained, which were related to both cytokine signaling and cell immune response. ARF suppressed IL-1β–induced expression of EGFR, MMP 9, IL2, MAPK14, and KDR in the HFLS-RA .Conclusions: ARF has good druggability and high exploitation potential. Methyl salicylate glycosides and flavonoids play essential roles in attuning RA. ARF may partially attenuate RA by regulating the expression of multi-targets in the inflammation–immune system. These provide valuable information to rationalize ARF and other TC/EMs in the treatment of RA.

Renoprotective Influence of Pomegranate Juice on Nephrotoxicity Induced by Methotrexate

Methotrexate (Metho) is cytotoxic drug widely used to treat malignant (lymphoma, leukemia, breast cancer) and non-malignant (rheumatic arthritis) diseases. It mediates nephrotoxicity via cellular oxidative stress. Pomegranate juice (POJ) has a potent antioxidant property. This research aimed to assess the potential protective effect of POJ against Metho-induced renal damage in rats. Renal toxicity was induced through intraperitoneal (ip) injection with a single dose of Metho (20 mg/kg). Forty male rats were randomly segregated into 4 groups; each group contained 10 rats. Control (Cont); Metho: rats on the 23rd day injected ip with Metho; POJ (2 ml/kg) +Metho: rats given POJ (2 ml/kg) orally once a day, and on the 23th day injected with Metho ip; and POJ (4 ml/kg) + Metho: rats given POJ (4 ml/kg) orally once a day, and on the 23th day rats were injected with Metho ip. After 5 days of Metho ip. injection, blood samples and renal tissue were obtained. Serum renal functions, ionic electrolytes (sodium and potassium), and pro-inflammatory cytokines were analyzed. Renal oxidative stress and antioxidant enzymes were also measured. Renal tissue were examined microscopically. Metho caused a significant increase in serum renal functions and disturbance in ionic electrolytes. As well as, there was a significant increase in pro-inflammatory cytokines and oxidative stress parameters, with detectable degenerative alteration in glomerulus and renal tissue changes compared with the Cont group. Pretreatment with POJ resulted in preventing biochemical and histopathological alterations induced by Metho. The high dose of POJ (4 ml/kg) was significantly more effective than low dose (2 ml/kg). In conclusion, POJ exerted a potent nephroprotective action and prevent Metho-induced nephrotoxicity. Therefore, POJ may has a beneficial effect in patients receiving Metho therapy.

A prospective observational study on efficacy of modified rheumatoid arthritis protocol of rituximab (2000 mg) on patients of pemphigus

<p class="abstract"><strong>Background:</strong> Rituximab (RTX), an anticluster of differentiation 20 antibody, targets B lymphocytes, has been shown in open series studies to be effective in treating pemphigus. The objective was to evaluate whether a modified rheumatoid arthritis protocol, in which the patient received four doses of 500 mg of rituximab at an interval of two weeks was safe and effective in pemphigus management.</p><p class="abstract"><strong>Methods:</strong> It was a prospective observational study in which 46 pemphigus patients included and four doses of 500 mg of RTX at an interval of two weeks given and number of doses required for complete remission (CR), proportion of patient respond partially or doesn’t respond or relapsed after CR.<strong></strong></p><p class="abstract"><strong>Results:</strong> We enrolled 46 patients in the study, 8 with pemphigus foliaceus (PF) and 38 with pemphigus vulgaris (PV). 20 were male and 26 were female followed up for 15±4.24 months (12-18). All patient responded to therapy. CR of 23 patient after 2 dose OF 500 mg RTX ,of 18 patient after 3 dose, 5 patient partial remission (PR) after 4 doses. All patient were on 100 mg OD azathioprine. PR, all have oral lesions got CR after 3 weeks of 4th dose. 3 patients relapsed MD 11±2.8 months (9-13 months) and given additional dose of 500 mg RTX and got resolved in 3 weeks.</p><p class="abstract"><strong>Conclusions:</strong> We found modified rheumatic arthritis protocol for RTX was shown to be effective in treatment of pemphigus patient and relapse cases with additional dose. Immunological assay were not performed to limit the study.</p><p class="abstract"> </p>

Circ_0025908 regulates cell vitality and proliferation via miR-137/HIPK2 axis of rheumatic arthritis

Background Rheumatic arthritis (RA) is an autoimmune disease with bad effects. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of RA, but the mechanism still indistinct. In this work, we explored the roles of circ_0025908 in RA. Methods The levels of circ_0025908, microRNA-137 (miR-137), and mRNA of homeodomain-interacting protein kinase 2 (HIPK2) were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in RA tissues. Meanwhile, the level of HIPK2 was quantified by Western blot analysis. Besides, the cell functions were examined by CCK8 assay, EdU assay, flow cytometry assay, ELISA, and Western blot. Furthermore, the interplay between miR-137 and circ_0025908 or HIPK2 was detected by dual-luciferase reporter assay. Results The levels of circ_0025908 and HIPK2 were upregulated, and the miR-137 level was decreased in RA tissues in contrast to that in normal tissues. For functional analysis, circ_0025908 deficiency inhibited cell vitality, cell mitotic cycle, cell proliferation, and immunoreaction in RA cells, whereas promoted cell apoptosis. Moreover, miR-137 was confirmed to repress the progression of RA cells by suppressing HIPK2. In mechanism, circ_0025908 acted as a miR-137 sponge to regulate the level of HIPK2. Conclusion Circ_0025908 facilitates the development of RA through increasing HIPK2 expression by regulating miR-137, which also offered an underlying targeted therapy for RA treatment.

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.

AB0899-HPR THE IMPACT OF CORONAVIRUS (COVID-19) PANDEMIC ON THERAPEUTIC MAINTENANCE IN PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES

Background:The Coronavirus pandemic caused many consequences on well being, access to care and therapeutic maintenance in patients with chronic diseases.Objectives:To assess the impact of COVID-19 on therapeutic maintenance of patients with Chronic Inflammatory Rheumatic Diseases (CIRD) and to identify related factors to difficulties in access to rheumatologist care during the COVID-19 pandemic.Methods:A cross-sectional study was conducted among patients with rheumatic diseases using a questionnaire providing information on patients and disease characteristics, impact of COVID-19 on access to rheumatologist care and therapeutic maintenance during the confinement. Reasons of therapeutic interruption and of diificulties in access to healthcare were precised.Results:We received answers from 350 patients (female sex of 68%, mean age of 46,1 ± 14,4 years) suffering from Chronic Inflammatory Rheumatic Diseases (CIRD):rheumatic arthritis (RA) (62.3%), spondyloarthropathies (34.3%), and undifferentiated CIRD (3.4%). The global average disease evolution was 12,1 ± 9,7 years.The patients were treated with conventional Disease-modifying anti-rheumatic drugs (cDMARDs) and biologic Disease-modifying anti-rheumatic drugs (bDMARDs) in respectively 67.4% and 30.6% of cases. Corticosteroids and Nonsteroidal Anti-Inflammatories (NSAIDs) intake was noted in 39.1 and 33.7% of patients.Difficulties to access to rheumatologist care appointments were reported in 82.9% of the participants. Reasons of thoses difficulties are summurized in Figure 1.Figure 1.Causes of difficulties of access to Rheumatologist care during COVID-19 pandemic.Half of patients declared that the pandemic had affected their therapeutic compliance. Discontinued drugs were in decreasing order: Synthetic antimalarials (68.4%), NSAIDs (45.8%), Methotrexate (43.8%), bDMARDs (25.2%), Sulfasalazine (18.2%) and Corticosteroids (10,2%).Causes of treatments interruption are summarized in Table I.Table 1.Causes of treatments interuption in patients with CIRDDrugsNot found in pharmaciesThe pharmacy refuses to give me the treatment without a recent prescriptionTo avoid the decrease in immunity and therefore to avoid catching Covid-19I stopped the follow-up, and so I stopped the treatment...Other reasonsNSAIDS027.874.144.427.8Corticosteroids014.392.957.150Methotrexate70.1310.416.422.4Sulfasalazine012.52575100Synthetic antimalarial69.20023.161.5Leflunomide00000bDMARDs07.440.744.451.9Conclusion:The COVID-19 pandemic impacted heavly on therapeutic maintenance in CIRD patients in our country. Patients expressed many difficulties in access to appropiate management. Facing to all thoses consequences, we need to devolopp as soon as possible adequate solutions adapted in such health crisis, especially therapeutic education and telemedecine.Disclosure of Interests:None declared